The goal of this application is to elucidate the role of SDF-1 on normal T cell differentiation and its disturbance in HIV infection. The investigator, Dr Christel Uittenbogaart, proposes that SDF-1 is responsible for the migration of CD34+ cells into the thymus and for the exit of mature T cells from the thymus. The proposal is based upon preliminary data that CXCR4 is expressed in immature thymocytes and late stage thymocytes and that SDF-1, the ligand for CXCR4, is produced in the corticomedullary junction in the human thymus. The proposal has two aims: 1) To elucidate the pattern of immigration and development of precursor T cells in the human thymus and exit of mature T cells from the thymus to the periphery and 2) to determine the effects of HIV infection on recruitment of precursor T cells and their exit into the periphery. The experimental systems will consist of in vitro chemotaxis assays and the scid-hu mouse model in which CD34+ cells will be injected, followed by examination of thymus tissue by immunohistochemistry, and of thymic and peripheral populations by flow cytometry. Thee effects of HIV on migration and recruitment will be elucidated using well characterized X4 and R5 HIV isolates.